1. Field of the Invention
The present invention relates to products based on polymers or copolymers substituted by groups able to give them a selective affinity with respect to products involved in the blood plasma coagulation process, such as thrombin and certain coagulation factors, such as VII and X factors. The invention also relates to a process for the preparation of products having these characteristics and the use of these products for the separation and purification of thrombin.
More specifically, the invention relates to products based on polymers or copolymers having in their chain substitutable groups, to which are statistically fixed groups X and Y, which give them special properties.
2. Description of the Prior Art
Polymers of this type, in which the groups X and Y have special anticoagulating properties have more particularly been described in French Pat. No. 2,461,724. In this patent, the anticoagulating property is obtained by fixing to the polymer, an amino acid derivative preferably having at least one free carboxyl function, such as glutamic acid. When the amino acid has several amino functions, it is necessary according to the aforementioned patent to block all the amino functions except one by a physiologically acceptable electroattractor group, such as benzyloxycarbonyl or tertiobutyloxycarbonyl, in order to obtain a satisfactory anticoagulating activity better than that of a polymer which is only sulphonated.
Although they have an anticoagulating activity, the products described in the aforementioned French Patent do not have a selective affinity for thrombin, because their effect on the blood plasma coagulation process is identical to that of heparin and consequently they act as a catalyst. Thus, with respect to thrombin, they do not have an affinity and selectivity of an adequate nature to permit their use as adsorbents in a thrombin separation and purification process.
In addition, molecules derived from L-arginine are known, which have an inhibiting activity to thrombin, as has been described by Okamoto et al, in the Journal of Medicinal Chemistry, 1980, Vol. 23, No. 8, pp. 827 to 836 and 1293 to 1299, said derivatives being in accordance with the following formula: ##STR1##
The influence of the radical R.sup.1 and the radical R.sup.2 on the activity of these products is investigated. However, these authors give no details of the possible affinity and selectivity of such products for thrombin.